Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/6894
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dc.contributor.advisorSeyrantepe, Volkanen_US
dc.contributor.authorTimur, Zehra Kevser-
dc.date.accessioned2018-04-16T13:52:31Z-
dc.date.available2018-04-16T13:52:31Z-
dc.date.issued2017-12-
dc.identifier.citationTimur, Z. K. (2017). Immunohistochemical, biochemical and imaging-mass spectrometric analysis of brain tissues of mice with combined deficiencies of β-hexosaminidase a, sialidase Neu4 and GM2-AP. Unpublished doctoral dissertation, İzmir Institute of Technology, İzmir, Turkeyen_US
dc.identifier.urihttp://hdl.handle.net/11147/6894-
dc.descriptionThesis (Doctoral)--Izmir Institute of Technology, Molecular Biology and Genetics, Izmir, 2017en_US
dc.descriptionFull text release delayed at author's request until 2019.01.18.en_US
dc.descriptionIncludes bibliographical references (leaves: 71-76)en_US
dc.descriptionText in English; Abstract: Turkish and Englishen_US
dc.description.abstractGangliosides are complex glycosphingolipids derived from glucosylceramide or galactosylceramide and contain sialic acid in their carbohydrate chain. Sialidases, known also as neurominidases, are a family of glycohydrolytic enzymes functioning in the catabolism of sialoglycoconjugates by removing α-glycosidically linked sialic acid residues. Sialidase Neu4 is the lysosomal sialidase and GM2 activator protein is the cofactor of β-Hexosaminidase a enzyme to degrade the GM2 ganglioside. The activity of sialidase Neu4 activity against GD1a and GM2 gangliosides were significantly increased by the co-transfection with GM2 activator protein to the cells transfected with sialidase Neu4. This in vitro study revealed that lipid-binding proteins can facilitate the glycolipid degradation rendered by sialidase Neu4 in the lysosomes. In the concept of this study, a systematic comparison of the storage levels of gangliosides, gene expression ratios and behavioral features of new double (Hexa-/-GM2AP-/- and GM2AP-/-Neu4-/-) and triple (Hexa-/-GM2AP-/-Neu4-/-) knockout mice models with the existing double (Neu4-/-Hexa-/-) and single (Hexa-/-) knockout models revealed the possible involvement of the GM2 activator protein as a cofactor of sialidase Neu4 in the bypass mechanism in the Tay-Sachs mice, in vivo. Based on the increased GM2 ganglioside level in brain and cerebellum detected by the immunohistochemical and imaging mass spectrometric analysis, we speculate that the sialidase Neu4 functions on the degradation of GM2 ganglioside with GM2 activator protein, in vivo.en_US
dc.description.abstractGangliositler glukozilseramit veya galactozilseramitten türemiş ve karbonhidrat zincirlerinde sialik asit taşııyan karmaşık glukosfingolipitlerdir. Sialidazlar, nörominidazlar olarak da bilinirler, sialoglukokonjugatlardan α-glukozidik olarak bağlı sialik asit gruplarını ayırarak aktivite gösteren glikohidrolitik enzim ailesindendirler. Sialidaz Neu4 lizozomal sialidazdır ve GM2 aktivatör protein ise β-Hekzosaminidaz a enziminin GM2 gangliositini yıkmak için olan kofaktörüdür. Sialidaz Neu4’ün GD1a ve GM2 gangliositlerine karşı olan aktivitesi sailidaz Neu4 aktarılan hücrelere GM2 aktivatör proteinin de birlikte aktarılması ile belirgin bir şekilde artmışır. Bu in vitro çalışma lipit bağlayan proteinlerin lizozomlardan sialidaz Neu4 ile gerçekleşirilen glikolipid yıkımını kolaylaştırdığını ortaya koymuştur. Bu çalışma kapsamında, yeni ikili Hexa-/-GM2AP-/- ve GM2AP-/-Neu4-/-) ve üçlü (Hexa-/-GM2AP-/-Neu4-/-) enzim eksikliği olan fare modellerinin, hali hazırda bulunan ikili (Neu4-/-Hexa-/-) ve tekli (Hexa-/-) enzim eksikliği olan fare modelleriyle, gangliositlerin birikim miktarlarının, gen ifadesi oranlarının ve davranışal özelliklerinin sistematik olarak karşlaşırılması, Tay-Sachs faresinde görülen metabolik baypas mekanizmasında GM2 aktivatör proteininin sialidaz Neu4’ün olası kofaktörü olarak katılmasını in vivo olarak ortaya çıkarmıştır. İmmunohistokimyasal ve görüntülü kütle spektrometrik analiz ile saptanan beyin ve beyincikte artan GM2 gangliosit miktarına bağlı olarak, sialidaz Neu4’ün in vivo olarak GM2 gangliositinin yıkımında GM2 aktivatör protein ile birlikte rol aldığını speküle ediyoruz.en_US
dc.description.sponsorshipThe Scientific and Technological Research Council of Turkey (TUBITAK) (113T025)en_US
dc.format.extentxiv, 76 leavesen_US
dc.language.isoenen_US
dc.publisherIzmir Institute of Technologyen_US
dc.relationinfo:eu-repo/grantAgreement/TUBITAK/TBAG/113T025en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectGangliosidesen_US
dc.subjectGM2 activator proteinen_US
dc.subjectGM2 gangliosideen_US
dc.subjectTay-Sachsen_US
dc.subjectSialidasesen_US
dc.titleImmunohistochemical, biochemical and imaging-mass spectrometric analysis of brain tissues of mice with combined deficiencies of ß-hexosaminidase a, sialidase Neu4 and GM2-apen_US
dc.title.alternativeβ-hekzosaminidaz A, sialidaz Neu4 ve Gm2-AP birleşik eksikliği bulunan fare beyin dokularının immünohistokimyasal, biyokimyasal ve görüntülü-kütle spektrometrik analizien_US
dc.typeDoctoral Thesisen_US
dc.institutionauthorTimur, Zehra Kevser-
dc.departmentThesis (Doctoral)--İzmir Institute of Technology, Molecular Biology and Geneticsen_US
dc.request.emailzehrapekmezi@gmail.com-
dc.request.fullnameZehra Kevser Timur-
dc.relation.publicationcategoryTezen_US
item.openairetypeDoctoral Thesis-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextopen-
item.fulltextWith Fulltext-
item.languageiso639-1en-
item.cerifentitytypePublications-
crisitem.author.dept01.01. Units Affiliated to the Rectorate-
Appears in Collections:Phd Degree / Doktora
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